Picoberin is a highly potent (low picomolar) inhibitor of purmorphamine- and Sonic Hedgehog (Shh)-induced osteogenesis with IC50 of 3 pM, acts as an AhR agonist and induces the expression of AhR target genes, thereby suppressing osteoblast differentiation.
Picoberin dose-dependently inhibited the expression of the alkaline phosphatase gene Alpl and suppressed bone mineralization, did not affect cell viability at concentrations up to 10 uM.
Picoberin neither modulated the expression of Hh target genes Ptch1, Gli1, and Gli2 nor altered GLI2/3-dependent reporter gene activity using Shh-LIGHT2 cells, did not target canonical Hh signaling.
Picoberin also inhibited Wnt3A-induced osteoblast differentiation of C3H10T1/2 cells.
Picoberin dose-dependently induced XRE-dependent reporter activity after 4 h in murine and human cell lines with EC50 values of 3.2 ± 2.7 nM in human hepatocellular carcinoma HepG2 cells, 58 ± 23 pM in murine embryonic fibroblasts (NIH-3T3 cells), 0.7 ± 0.3 nM in human fibroblasts (HaCaT), and 71.2 ± 35.6 nM in murine hepatoma cells (Hepa-1c1c7).
Picoberin dose-dependently decreased AhR protein levels in HepG2 cells after 4 h.